Therapeutic management of a chronic painful syndrome such as fibromyalgia (FM) lacks effective and safe single or combined analgesics. Current medications such as gabapentin (GPB) or pregabalin are moderately effective but in the presence of several adverse effects. Natural products derived from cruciferous vegetables such as sulforaphane (SFN) produce neuroprotective effects due to their potent antioxidant and anti-inflammatory properties. However, it is unknown whether positive or negative pharmacological interactions may occur when GBP and SFN are combined. The aim of this study was to estimate the pharmacological interaction of GBP and SFN in FM-like pain induced in rats. Time course curves of antiallodynic and antihyperalgesic effects were constructed for both SFN (3.16, 31.6, and 100 mg/kg, i.p.) and GBP (10, 31.6, and 100 mg/kg, i.p.) by recording behavioral responses every 30 min and up to 4 h afterward, from which dose-response effects were also obtained to decide the dosage combination. An electrocorticographic (ECoG) recording in mice and docking analysis were also explored to explain the pharmacological interaction. Our results demonstrated significant and dose-dependent antiallodynic and antihyperalgesic effects in their individual administration. While a combination of intermediate doses of these drugs enhanced their effects producing the same level as that obtained by using only 1/3 of the individual dose in each case. The ECoG recording and docking analysis suggest that calcium channels could be partly involved in the drug interaction. This study provides preclinical evidence that SFN alone and in combination with GBP may be beneficial for relieving FM-like pain at certain doses.
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http://dx.doi.org/10.1016/j.biopha.2025.117929 | DOI Listing |
Cells
March 2025
Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University (Unesp), Botucatu 18618-689, São Paulo, Brazil.
Ovarian cancer (OC) is characterized by high mortality rates due to late diagnosis, recurrence, and metastasis. Here, we show that extracellular signaling molecules secreted by adipose-derived mesenchymal stem cells (ASCs) and OC cells-either in the conditioned medium (CM) or within small extracellular vesicles (sEVs)-modulate cellular responses and drive OC progression. ASC-derived sEVs and CM secretome promoted OC cell colony formation, invasion, and migration while upregulating tumor-associated signaling pathways, including TGFβ/Smad, p38MAPK/ERK1/2, Wnt/β-catenin, and MMP-9.
View Article and Find Full Text PDFCells
February 2025
Faculty of Sport Sciences, Waseda University, Tokorozawa 359-1192, Japan.
Background: Skeletal muscle wasting is commonly observed in aging, immobility, and chronic diseases. In pathological conditions, the impairment of skeletal muscle and immune system often occurs simultaneously. Recent studies have highlighted the initiative role of skeletal muscle in interactions with immune cells.
View Article and Find Full Text PDFNucleic Acids Res
February 2025
Protein-Nucleic Acid Interaction Section, Center for Structural Biology, Center for Cancer Research, National Cancer Institute, Frederick, MD, 21702, United States.
Synthetic RNA devices are engineered to control gene expression and offer great potential in both biotechnology and clinical applications. Here, we present multidisciplinary structural and biochemical data for a tetracycline (Tc)-responsive RNA device (D43) in both ligand-free and bound states, providing a structure-dynamical basis for signal transmission. Activation of self-cleavage is achieved via ligand-induced conformational and dynamical changes that stabilize the elongated bridging helix harboring the communication module, which drives proper coordination of the catalytic residues.
View Article and Find Full Text PDFArch Pharm (Weinheim)
March 2025
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Bezmialem Vakif University, Istanbul, Türkiye.
This study investigates the anticholinesterase (acetylcholinesterase [AChE] and butyrylcholinesterase [BChE]) and carbonic anhydrase (CAI and CAII) inhibitory activities of carnosic acid and its natural derivatives, including carnosol, rosmanol, 7-methoxy-rosmanol, 12-methoxy-carnosic acid, and isorosmanol. Among the tested compounds, rosmanol demonstrated exceptional potency, with IC values of 0.73 nM for AChE and 0.
View Article and Find Full Text PDFJ Cell Sci
March 2025
BRIC-National Centre for Cell Science, S.P. Pune University Campus, Ganeshkhind, Pune-411007, India.
P-bodies (PBs) and stress granules (SGs) are conserved, non-membranous cytoplasmic condensates of RNA-protein complexes. PBs are implicated in post-transcriptional regulation of gene expression through mRNA decay, translational repression and/or storage. Although much is known about the de novo formation of PBs and SGs involving liquid-liquid phase separation through multiple protein-protein and protein-RNA interactions, their subcellular localization and turnover mechanisms are less understood.
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